1. High-sucrose diets contribute to brain angiopathy with impaired glucose uptake and psychosis-related higher brain dysfunctions in mice
- Author
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Takuya Sakamoto, Hiroko Shimbo, Seiji Shioda, Tomoya Nakamachi, Yasumasa Nishito, Hideki Miwa, Junjiro Horiuchi, Toshio Miyata, Yasuto Kunii, Atsuko Nagaoka, Toshifumi Tomoda, Mitsuhiro Miyashita, Takatoshi Hikida, Hirooki Yabe, Haruo Okado, Takashi Dan, Ryuta Izumi, Makoto Arai, Masanari Itokawa, Kazuhiro Suzuki, Mizuki Hino, Kazuya Toriumi, Tomoko Tanaka, and Shinobu Hirai
- Subjects
High sucrose ,Psychosis ,medicine.medical_specialty ,Multidisciplinary ,business.industry ,Glucose uptake ,Brain dysfunction ,SciAdv r-articles ,Life Sciences ,macromolecular substances ,medicine.disease ,Angiopathy ,Pathogenesis ,Endocrinology ,Internal medicine ,mental disorders ,medicine ,business ,Research Article ,Neuroscience - Abstract
Description, High-sugar diet in adolescence induces neural angiopathy and multiple psychiatric endophenotypes with impaired glucose logistics., Metabolic dysfunction is thought to contribute to the severity of psychiatric disorders; however, it has been unclear whether current high–simple sugar diets contribute to pathogenesis of these diseases. Here, we demonstrate that a high-sucrose diet during adolescence induces psychosis-related behavioral endophenotypes, including hyperactivity, poor working memory, impaired sensory gating, and disrupted interneuron function in mice deficient for glyoxalase-1 (GLO1), an enzyme involved in detoxification of sucrose metabolites. Furthermore, the high-sucrose diet induced microcapillary impairments and reduced brain glucose uptake in brains of Glo1-deficient mice. Aspirin protected against this angiopathy, enhancing brain glucose uptake and preventing abnormal behavioral phenotypes. Similar vascular damage to our model mice was found in the brains of randomly collected schizophrenia and bipolar disorder patients, suggesting that psychiatric disorders are associated with angiopathy in the brain caused by various environmental stresses, including metabolic stress.
- Published
- 2021